Hubbry Logo
TopiramateTopiramateMain
Open search
Topiramate
Community hub
Topiramate
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Contribute something
Topiramate
Topiramate
Topiramate
View on Wikipedia
from Wikipedia

Topiramate
Clinical data
Trade namesTopamax, Trokendi XR, Qudexy XR, others
Other namesTopiramic acid
AHFS/Drugs.comMonograph
MedlinePlusa697012
License data
Pregnancy
category
  • AU: D
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability80%
Protein binding13–17%; 15–41%
MetabolismLiver (20–30%)
Elimination half-life21 hours
ExcretionUrine (70–80%)
Identifiers
  • 2,3:4,5-Bis-O-(1-methylethylidene)-β-D-fructopyranose sulfamate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.129.713 Edit this at Wikidata
Chemical and physical data
FormulaC12H21NO8S
Molar mass339.36 g·mol−1
3D model (JSmol)
  • O=S(=O)(OC[C@@]21OC(O[C@H]1[C@@H]3OC(O[C@@H]3CO2)(C)C)(C)C)N
  • InChI=1S/C12H21NO8S/c1-10(2)18-7-5-16-12(6-17-22(13,14)15)9(8(7)19-10)20-11(3,4)21-12/h7-9H,5-6H2,1-4H3,(H2,13,14,15)/t7-,8-,9+,12+/m1/s1 checkY
  • Key:KJADKKWYZYXHBB-XBWDGYHZSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Topiramate, sold under the brand name Topamax among others, is an oral medication used to treat epilepsy and prevent migraines.[8] For epilepsy, this includes treatment for generalized or focal seizures.[9] It has also been used off-label for alcohol dependence and essential tremor.[8]

Common side effects include tingling, feeling tired, loss of appetite, abdominal pain, weight loss,[10] and decreased cognitive function such as trouble concentrating.[8][9] Serious side effects may include suicidal ideation, increased ammonia levels resulting in encephalopathy, and kidney stones.[8] Topiramate can cause birth defects, including cleft lip and palate.[11] Risks/benefits should be carefully discussed with the full treatment team. Topiramate is considered "probably compatible" with lactation and is not contraindicated for breastfeeding, though monitoring of the infant for diarrhea or poor weight gain may be considered.[12][13] Its mechanism of action is unclear.[8]

Topiramate was approved for medical use in the United States in 1996.[8] It is available as a generic medication.[9][14][15] In 2023, it was the 71st most commonly prescribed medication in the United States, with more than 9 million prescriptions.[16][17]

Medical uses

[edit]
A package of topiramate 25mg from Norway

Topiramate is used to treat epilepsy in children and adults, and it was originally used as an anticonvulsant.[18] In children, it is indicated for the treatment of Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delay. It is most frequently prescribed for the prevention of migraines,[18] as it decreases the frequency of attacks.[19][20] Topiramate is used to treat medication overuse headache and is recommended by the European Federation of Neurological Societies as one of the few medications showing effectiveness for this indication.[21]

Pain

[edit]

A 2018 review found topiramate of no use in chronic low back pain.[22] Topiramate has not been shown to work as a pain medicine in diabetic neuropathy, the only neuropathic condition for which it has been adequately tested.[23]

Other

[edit]

One common off-label use for topiramate is in the treatment of bipolar disorder.[24][25][26] A review published in 2010 suggested a benefit of topiramate in the treatment of symptoms of borderline personality disorder; however, the authors noted that this was based only on one randomized controlled trial and requires replication.[27]

Topiramate has been used as a treatment for alcoholism.[28] The U.S. Veterans Affairs and Department of Defense 2015 guidelines on substance use disorders list topiramate as a "strong for" in its recommendations for alcohol use disorder.[29]

Other uses include treatment of obesity[30][31] and binge eating disorder,[32] and off-setting weight gain induced by taking antipsychotic medications.[33] In 2012, the combination of phentermine/topiramate was approved in the United States for weight loss.

Adverse effects

[edit]

People taking topiramate should be aware of the following risks:

  • Avoid activities requiring mental alertness and coordination until drug effects are realized.
  • Topiramate may impair heat regulation,[34] especially in children. Use caution with activities leading to an increased core temperature, such as strenuous exercise, exposure to extreme heat, or dehydration.
  • Topiramate may cause visual field defects.[35]
  • Topiramate may decrease the effectiveness of oestrogen-containing oral contraceptives.
  • Taking topiramate in the first trimester of pregnancy may increase the risk of cleft lip/cleft palate in infants.[36]
  • As is the case for all antiepileptic drugs, it is advisable not to suddenly discontinue topiramate, as there is a theoretical risk of rebound seizures.
  • Some studies have attributed loss of appetite and upper respiratory tract infection to topiramate, but studies have concluded these adverse events are not difficult to tolerate for most individuals.[37]

Frequency

[edit]

Adverse effects by incidence:[38][39][40][41]

Very common (>10% incidence) adverse effects include:

Rarely, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance.[42]

The U.S. Food and Drug Administration (FDA) has notified prescribers that topiramate can cause acute myopia and secondary angle closure glaucoma in a small subset of people who take topiramate regularly.[43] The symptoms, which typically begin in the first month of use, include blurred vision and eye pain. Discontinuation of topiramate may halt the progression of the ocular damage and may reverse the visual impairment.

Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations.[44] This might be particularly important for women who take topiramate to prevent migraine attacks. In March 2011, the FDA notified healthcare professionals and patients of an increased risk of development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with Topamax (topiramate) during pregnancy and placed it in Pregnancy Category D.[36]

Cognitive and word-finding difficulties, which may occur in some patients, may respond to piracetam.[45][46]

Carbonation dysgeusia (distortion of the sense of taste-sensation of carbonation) may respond to and/or be prevented with zinc.[47]

Topiramate has been associated with a statistically significant increase in suicidality,[48] and "suicidal thoughts or actions" is now listed as one of the possible side effects of the drug "in a very small number of people, about 1 in 500."[34][49]

Overdose

[edit]

Symptoms of acute and acute on chronic exposure to topiramate range from asymptomatic to status epilepticus, including in patients with no seizure history.[50][51] In children, overdose may also result in hallucinations.[51] Topiramate has been deemed the primary substance that led to fatal overdoses in cases that were complicated by polydrug exposure.[52] The most common signs of overdose are dilated pupils, somnolence, dizziness, psychomotor agitation, and abnormal, uncoordinated body movements.[50][51][52]

Interactions

[edit]

Topiramate has many drug-drug interactions. Some of the most common are listed below:

Pharmacology

[edit]
Chair-style representation of skeletal formula

The topiramate molecule is a sulfamate modified sugar – more specifically, fructose diacetonide, an unusual chemical structure for a pharmaceutical.

Topiramate is quickly absorbed after oral use. It has a half-life of 21 hours and a steady state of the drug is reached in 4 days in patients with normal renal function.[55] Most of the drug (70%) is excreted in the urine unchanged. The remainder is extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose.

Several cellular targets have been proposed to be relevant to the therapeutic activity of topiramate.[56] These include voltage-gated sodium channels, high-voltage-activated calcium channels, GABAA receptors, AMPA/kainate receptors, and carbonic anhydrase isoenzymes. There is evidence that topiramate may alter the activity of its targets by modifying their phosphorylation state instead of by direct action.[57] The effect on sodium channels could be of particular relevance for seizure protection. Although topiramate does inhibit high-voltage-activated calcium channels, its relevance to clinical activity is uncertain. Effects on specific GABAA receptor isoforms could also contribute to the anticonvulsant activity of the drug. Topiramate selectively inhibits cytosolic (type II) and membrane-associated (type IV) forms of carbonic anhydrase. Its action on carbonic anhydrase isoenzymes may contribute to the drug's side effects, including its propensity to cause metabolic acidosis and calcium phosphate kidney stones.[citation needed]

Topiramate inhibits maximal seizure activity in electroconvulsive therapy and in pentylenetetrazol-induced seizures as well as partial and secondarily generalized tonic-clonic seizures in the kindling model, findings predictive of a broad spectrum of activities clinically. Its action on mitochondrial permeability transition pores has been proposed as a mechanism.[58]

While many anticonvulsants have been associated with apoptosis in young animals, animal experiments have found that topiramate is one of the very few anticonvulsants that do not induce apoptosis in young animals at doses needed to produce an anticonvulsant effect.[59]

Detection in body fluids

[edit]

Blood, serum, or plasma topiramate concentrations may be measured using immunoassay or chromatographic methods to monitor therapy, confirm a diagnosis of poisoning in hospitalized patients, or assist in a medicolegal death investigation. Plasma levels are usually less than 10 mg/L during therapeutic administration, but can range from 10 to 150 mg/L in overdose victims.[60][61][62]

History

[edit]

Topiramate was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil Pharmaceuticals.[63][64] Topiramate was first sold in 1996.[65] Mylan Pharmaceuticals was granted final approval by the FDA for the sale of generic topiramate in the United States and the generic version was made available in September 2006.[66] The last patent for topiramate in the U.S. was for use in children and expired on 28 February 2009.[67]

Research

[edit]

Topiramate is being studied as a potential treatment for post-traumatic stress disorder (PTSD).[68]

There is some evidence for the use of topiramate in the management of cravings related to withdrawal from dextromethorphan.[69]

A 2023 systematic review of seizure treatment for infants aged 1 to 36 months identified three studies that evaluated the use of topiramate. Though its adverse effects, including upper respiratory tract infection and loss of appetite, were rarely severe enough for the medication to be discontinued in this age group, its effectiveness in reducing seizures was inconclusive. The available research suffers from small sample sizes, inconsistent findings, and inadequate comparison groups.[70]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Topiramate

View on Grokipedia
from Grokipedia
Topiramate is a sulfamate-substituted and second-generation antiepileptic drug that acts through multiple mechanisms to reduce neuronal excitability, including voltage-gated blockade, enhancement of gamma-aminobutyric acid (GABA) activity, antagonism of glutamate receptors, and inhibition of enzymes. It was first approved by the U.S. in 1996 for the treatment of in patients aged 2 years and older, either as monotherapy or adjunctive therapy for partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome. In 2004, the FDA approved it for the prophylaxis of headaches in adults; this indication was expanded in 2014 to include adolescents aged 12 years and older, though it is not indicated for acute migraine treatment. Additionally, in 2012, topiramate was approved in combination with phentermine (as Qsymia) for chronic in adults with or overweight conditions accompanied by weight-related comorbidities, based on its appetite-suppressing effects and promotion of . The is available in various oral formulations, including immediate-release tablets, sprinkle capsules, extended-release capsules, and oral solutions, with a of over 80% and a of approximately 21 hours, primarily excreted unchanged by the s. Topiramate's broad therapeutic profile has led to off-label uses in conditions such as , , , and , though these applications require careful consideration due to potential adverse effects like , , , kidney stones, and increased risk of . Originally discovered in the during research for antidiabetic agents, topiramate's development as an marked a significant advancement in management, offering efficacy across a wide range of with relatively fewer drug interactions compared to first-generation antiepileptics.

Medical Uses

Epilepsy

Topiramate is approved for use as initial monotherapy in patients aged 2 years and older with partial-onset seizures or primary generalized tonic-clonic seizures, as well as adjunctive therapy for partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome in the same age group. These indications are supported by clinical trials demonstrating its broad-spectrum antiepileptic activity through mechanisms including blockade, enhancement of GABA activity, and antagonism of glutamate receptors. Dosing typically begins at 25-50 mg per day for adults, titrated weekly by 25-50 mg increments to a of 200-400 mg per day, divided into two doses, depending on seizure type and response. In children aged 2-16 years, initial dosing is weight-based at 5-9 mg/kg per day, similarly titrated to a maintenance of 5-9 mg/kg per day, with adjustments to avoid exceeding adult-equivalent exposures. Pivotal randomized controlled trials (RCTs) established , showing median reductions of 27-48% for partial-onset seizures in adults (versus 12% for ) and 33% in children (versus 11% for ), with responder rates (≥50% reduction) of 24-46% in adults and 39% in children. For primary generalized tonic-clonic s, RCTs reported a 57% median reduction (versus 9% ), and for Lennox-Gastaut syndrome, a 15% reduction in drop attacks (versus a 5% increase for ). Long-term efficacy data from open-label extensions of these RCTs indicate sustained control over 1-2 years, with over 50% of patients achieving at least 50% reduction and approximately 10-11% becoming -free for periods exceeding 6 months. In pediatric populations, topiramate demonstrates a comparable safety profile to adults when dosed appropriately, with common adverse effects including and anorexia, though cognitive and behavioral effects require monitoring; RCTs confirm tolerability as adjunctive , with 47% responder rates in cases.

Migraine Prevention

Topiramate is approved by the U.S. (FDA) for the preventive treatment of in adults, with a recommended of 100 mg per day administered as 50 mg twice daily. Treatment typically begins with a schedule starting at 25 mg once daily for the first week, increasing to 25 mg twice daily in the second week, 50 mg twice daily in the third week, and reaching the target dose of 100 mg per day (50 mg twice daily) by the fourth week to minimize side effects. This dosing regimen allows for gradual adjustment while achieving therapeutic levels for migraine prophylaxis. Clinical evidence from randomized controlled trials (RCTs) supports topiramate's efficacy in reducing frequency compared to . In a pivotal 2004 double-blind RCT involving 483 adults with episodic , topiramate at 100 mg per day resulted in a 50% or greater reduction in monthly frequency (responder rate) in approximately 50% of patients, compared to 26% in the group, alongside a mean reduction of 2.1 monthly attacks from baseline. These findings were consistent across secondary outcomes, including reductions in days and severity, establishing topiramate as an effective option for prevention in adults. For adolescents aged 12 to 17 years, topiramate is also FDA-approved for prevention, typically at lower doses of 50 to 100 mg per day following a similar approach adjusted for body weight. A randomized, double-blind, -controlled study in 157 pediatric patients demonstrated that topiramate at 100 mg per day significantly reduced the mean monthly attack rate by 2.4 attacks compared to (p=0.038), though the 50 mg per day dose did not show . This supports its use in this population for prophylactic therapy. A 2025 phase 3 head-to-head trial (TEMPLE study) compared topiramate to the newer atogepant in adults with episodic or chronic , revealing higher discontinuation rates with topiramate due to adverse events. Over 24 weeks, 29.6% of topiramate-treated patients discontinued treatment because of adverse events, compared to 12.1% in the atogepant group, highlighting tolerability challenges that may impact long-term adherence in migraine prevention.

Weight Management

Topiramate is approved by the U.S. (FDA) in combination with phentermine as Qsymia for chronic weight management in adults with an initial (BMI) of ≥30 kg/m² or ≥27 kg/m² in the presence of at least one weight-related , such as , mellitus, or , as an adjunct to a reduced-calorie diet and increased . This approval was granted on July 17, 2012, based on pivotal phase 3 trials demonstrating clinically meaningful weight reduction. In these studies, patients on the recommended of 7.5 mg phentermine/46 mg topiramate extended-release once daily achieved an average of approximately 9-10% of baseline body weight over 56 weeks, compared to 1-2% with , with 62-70% of patients achieving at least 5% weight loss. The dosing regimen typically begins at 3.75 mg phentermine/23 mg topiramate extended-release once daily for 14 days, titrating to 7.5 mg/46 mg, and potentially escalating to 15 mg/92 mg if additional loss is needed and tolerated. As monotherapy, topiramate is used off-label for , particularly in patients with or with comorbidities, though it lacks formal FDA approval for this indication. Clinical trials have shown that topiramate monotherapy leads to an average body weight reduction of 5-10% over 6-12 months, with dose-ranging studies reporting mean losses of 5-6.3% at 24 weeks on doses of 96-192 mg daily. Sustained weight loss has been observed in longer-term studies, with benefits maintained through 12 months in responsive patients when combined with interventions. Topiramate contributes to primarily through appetite suppression and metabolic effects, including modulation of neurotransmitters such as gamma-aminobutyric acid (GABA) and glutamate to enhance and reduce food cravings, as well as potential alterations in that decrease caloric intake. It also promotes metabolic improvements, such as reduced fat accumulation and lowered levels, supporting sustained weight reduction in 6-12 month trials. These mechanisms have led to brief in off-label contexts like , where is a secondary outcome.

Off-Label Uses

Topiramate has been investigated for the off-label treatment of alcohol use disorder, where randomized controlled trials (RCTs) demonstrate its efficacy in reducing heavy drinking. In a multicenter, double-blind RCT involving 371 alcohol-dependent individuals, topiramate titrated to 300 mg/day over 6 weeks significantly reduced the percentage of heavy drinking days by 16.2% (95% CI, 10.8%-21.6%; P < .001) compared to , alongside decreases in drinks per drinking day and improvements in plasma γ-glutamyltransferase levels as a of alcohol consumption. A of seven RCTs further supports moderate efficacy (Hedges' g = 0.406, P < .01) for reducing heavy drinking and promoting abstinence, with typical dosing ranging from 100-300 mg/day. Emerging 2025 research also suggests potential benefits in alcohol use modulated by GRIK1 . Preliminary evidence from 2025 indicates topiramate's potential in managing use-related disorders, with reviews highlighting its role in substance use treatment alongside mood and anxiety benefits. As an adjunct in , topiramate shows limited evidence for mood stabilization from small-scale trials, though it is not considered first-line . A review of controlled studies indicates potential benefits in prophylaxis of mood episodes when added to standard treatments, but results are inconsistent across larger evaluations, with no robust support for acute or depression management. Dosing in these adjunctive contexts typically starts at 25-50 mg/day and titrates to 100-200 mg/day based on tolerability. For , studies from the 2010s provide limited but positive efficacy data, positioning topiramate as a second-line option after or . A 2015 meta-analysis of RCTs found topiramate superior to in reducing total scores (mean difference -8.58, 95% CI -15.46 to -1.70; P < .05), with common dosing of 50-400 mg/day divided twice daily. Similarly, for , 2010s investigations reveal limited efficacy, particularly in , where a Cochrane review of available trials concluded no clear benefit over despite some symptom reduction in small cohorts. In , phase 3-level multicenter RCTs support topiramate's role in reducing binge episodes, often at doses of 75-200 mg/day. A double-blind, -controlled with 61 obese participants with showed significant decreases in binge frequency (from 4.7 to 1.3 episodes/week vs. 4.5 to 3.6 with ; P < .001) and body weight after 16 weeks of treatment up to 200 mg/day. Ongoing research explores topiramate's potential in , with preliminary suggesting possible reductions in symptoms when used adjunctively.

Contraindications and Precautions

Pregnancy and Reproductive Risks

Topiramate is contraindicated during due to an increased risk of congenital malformations in the offspring, particularly oral clefts. Data from the U.S. (FDA) in 2011 indicated that exposure to topiramate early in is associated with a 2- to 5-fold increased risk of oral clefts compared to the general population. Specifically, the prevalence of oral clefts was reported as 1.4% in infants exposed to topiramate monotherapy, versus 0.38% in unexposed infants. Overall, the risk of major congenital malformations with first-trimester exposure ranges from 1.4% to 2.5%, exceeding the baseline population risk of approximately 0.7%. In the United States, the FDA recommends that women of childbearing potential use effective contraception during topiramate treatment and that the benefits be weighed against fetal risks, but does not mandate a formal Pregnancy Prevention Programme. To mitigate these teratogenic risks, regulatory authorities in other regions have implemented strict preventive measures for women of childbearing potential. In 2024, the European Medicines Agency (EMA) and the UK's Medicines and Healthcare products Regulatory Agency (MHRA) introduced a Pregnancy Prevention Programme (PPP) for topiramate, making it contraindicated in pregnancy and in women who could become pregnant unless specific conditions are met. Under the PPP, prescribers must confirm a negative pregnancy test prior to initiation, ensure the use of highly effective contraception throughout treatment, and conduct monthly pregnancy monitoring. Patients receive education on the risks, and treatment discontinuation is required if pregnancy occurs. Topiramate may also impact and reproductive health in women. It has been associated with menstrual irregularities, including irregular periods and breakthrough bleeding, potentially due to its effects on hormonal balance. Additionally, at doses greater than 200 mg/day, topiramate may reduce the efficacy of hormonal contraceptives, such as combined oral contraceptives, by accelerating their metabolism, potentially increasing the risk of ; however, at lower doses used for prevention, studies indicate no increased risk of unintended pregnancies. Women using topiramate are advised to employ alternative or additional non-hormonal contraception methods as part of risk management. In 2025, Medsafe in issued updates reinforcing these precautions, particularly for prophylaxis. Topiramate is now explicitly contraindicated for prevention in women of childbearing potential unless no suitable alternatives exist and the PPP conditions are strictly followed, emphasizing the need to avoid exposure in fertile women to prevent fetal harm such as and other malformations.

Other Contraindications

Topiramate is contraindicated in patients with known to the drug itself. Although topiramate is a sulfamate-substituted derivative structurally related to s, with allergies is not established as an absolute , but caution is advised in such cases due to potential reactions. Topiramate carries a risk of inducing acute and secondary angle-closure through mechanisms involving choroidal effusion and , typically occurring within the first month of therapy; patients with a history of acute angle-closure should be monitored closely or alternative therapy considered. Discontinuation is recommended if symptoms such as ocular pain or develop. In cases of severe hepatic impairment, topiramate requires caution despite no routine dose adjustment, as reduced hepatic function may increase the risk of and other metabolic disturbances; levels should be monitored. For renal impairment ( clearance <70 mL/min/1.73 m²), the recommended starting dose is half of the usual dose, with slower to maintenance levels based on tolerability. Topiramate is contraindicated or requires extreme caution in patients predisposed to , such as those with , severe respiratory disorders, or conditions involving renal loss, due to the drug's inhibition of isoenzymes leading to hyperchloremic non-anion gap . Baseline and periodic serum monitoring is essential, with dose reduction or discontinuation considered if persists below 20 mEq/L. Elderly patients warrant special precautions with topiramate due to age-related declines in renal function, resulting in approximately 20% lower clearance, a 13% longer , and 25% higher systemic exposure compared to younger adults. Dose adjustments are recommended if clearance is below 70 mL/min/1.73 m², and the risk of falls increases due to potential adverse effects like and .

Adverse Effects

Common Adverse Effects

Topiramate is commonly associated with central nervous system and metabolic adverse effects, which occur in a significant proportion of patients during treatment for or prophylaxis. These effects are typically mild to moderate, dose-dependent, and often diminish with gradual dose titration or time. Clinical trials indicate that over 10% of patients experience , , , , anorexia, and , with incidences varying by indication, dose, and patient population. Paresthesia, characterized by tingling or numbness in the extremities or perioral region, is the most frequently reported , affecting 40% to 51% of adults in monotherapy trials (at 400 mg/day) and prophylaxis trials (at 100 mg/day), compared to 6% to 12% with . In pediatric populations, the incidence is lower, ranging from 4% to 19%. This sensory disturbance is often benign and dose-related, typically resolving upon dose reduction or discontinuation. is another prevalent effect, observed in 9% to 17% of patients across trials, with mean reductions of 2% to 6% of body weight; notably, 6% of adults in trials experienced at least 10% body weight loss versus 1% on . This can be beneficial for but requires monitoring in individuals or children to prevent growth impacts. Fatigue, dizziness, and somnolence are reported in 6% to 29% of patients, with higher rates (15% to 29%) in adjunctive epilepsy therapy at 200 to 400 mg/day. Cognitive slowing, including word-finding difficulties, psychomotor slowing, and concentration issues, occurs in 6% to 13% of adults, manifesting as "brain fog" or slowed verbal fluency; up to 10% of patients may report such symptoms overall, particularly at doses above 200 mg/day. Anorexia and nausea, which contribute to weight loss, affect 10% to 24% and 8% to 13% of patients, respectively, and are more pronounced during rapid titration but frequently resolve with slower dose escalation (e.g., weekly increments of 25 to 50 mg). Post-marketing surveillance confirms these effects occur in more than 10% of users, emphasizing the need for individualized dosing to improve tolerability. At higher doses, these common effects may intensify and transition toward more serious manifestations, necessitating close clinical monitoring. Management strategies include starting at low doses (25 mg/day) and titrating gradually over 4 to 8 weeks, alongside on symptom recognition and lifestyle adjustments like hydration to mitigate .

Serious Adverse Effects

Topiramate carries a for the risk of and behavior, implemented by the FDA in 2008 following a of antiepileptic drugs showing approximately a twofold increase in risk compared to (0.43% incidence in treated patients versus 0.24% in placebo). This class effect applies across indications, including and prevention, and patients should be monitored closely for emerging or worsening depression, unusual changes in mood or behavior, or suicidal thoughts, with immediate medical intervention recommended if observed. Metabolic acidosis is another serious adverse effect associated with topiramate, resulting from its inhibition of in the renal tubules, leading to a non-anion gap . Subclinical reductions in serum occur in 30-40% of patients, while symptomatic cases, defined by markedly low levels (e.g., <17 mEq/L), affect 1-3% and may manifest as , dyspnea, or cardiac arrhythmias. Monitoring of baseline and periodic serum levels is essential, with dose reduction or discontinuation advised if persistent acidosis develops to prevent complications such as or growth retardation in children. Topiramate increases the risk of nephrolithiasis (kidney stones) to 1-2% in adults, with a higher incidence of up to 7% in pediatric patients aged 1-24 months, due to urinary citrate reduction and acidic urine pH changes. A 2025 retrospective cohort study reported a 3-year cumulative incidence of symptomatic kidney stones of 2.9% in topiramate users versus 1.2% in non-users. Concomitant use with other carbonic anhydrase inhibitors or ketogenic diets exacerbates this risk, and preventive measures include maintaining high fluid intake (at least 8 glasses of water daily). Additionally, topiramate can cause oligohydrosis (reduced sweating) and hyperthermia, reported primarily in children and during hot weather or exercise, potentially leading to heatstroke if unrecognized. Patients should be advised to monitor for decreased perspiration and elevated body temperature, avoiding overheating environments. Acute visual disturbances, including secondary angle-closure and permanent defects, represent rare but vision-threatening effects of topiramate, often linked to idiosyncratic ciliochoroidal and myopic shifts. These typically occur within the first month of therapy and require immediate discontinuation to prevent irreversible damage, with symptoms such as , eye pain, or halos around lights warranting urgent ophthalmologic evaluation.

Overdose

Symptoms of topiramate overdose can include seizures, drowsiness or severe somnolence, speech difficulties, blurred or double vision, or trouble thinking, agitation, or loss of coordination, , , depression, loss of appetite, irregular heartbeat, fast or shallow breathing, and . In severe cases, it may lead to loss of consciousness or . There is no specific for topiramate overdose. involves supportive care, such as monitoring and stabilizing , treating symptoms (e.g., anticonvulsants for seizures), and providing general emergency medical support. is recommended for severe or cases to enhance drug elimination, as topiramate is dialyzable. Patients or caregivers should immediately contact poison control (e.g., 1-800-222-1222 in the ) or emergency services if overdose is suspected.

Drug Interactions

Topiramate interacts with various medications, primarily through effects on enzymes, renal excretion, and inhibition, which can alter drug levels, efficacy, or increase adverse effects. Clinicians should monitor patients and adjust doses as needed.

Antiepileptic Drugs

Concomitant use with other antiepileptic drugs (AEDs) requires caution:

Hormonal Contraceptives

Topiramate reduces the efficacy of estrogen-containing oral contraceptives, particularly at doses greater than 200 mg/day, by increasing clearance (18-30% decrease in levels), leading to breakthrough bleeding and risk of . Use alternative non-hormonal contraception or higher-dose formulations.

Carbonic Anhydrase Inhibitors and Metformin

  • Other inhibitors (e.g., , zonisamide) increase the risk of and nephrolithiasis; avoid concomitant use if possible and monitor acid-base balance.
  • Metformin exposure increases (AUC by 25%), and topiramate's risk of causing may contraindicate metformin use in affected patients; assess clinical significance and monitor for .

Central Nervous System Depressants

Topiramate may enhance CNS depression when used with alcohol, benzodiazepines, or other sedatives, increasing risks of drowsiness and impaired coordination; advise caution.

Other Significant Interactions

  • Lithium: Increases lithium systemic exposure (AUC by 26%) at topiramate doses up to 600 mg/day; monitor lithium levels.
  • Hydrochlorothiazide: Increases topiramate exposure (AUC by 29%) and may cause hypokalemia; dose reduction of topiramate may be required.
  • Pioglitazone: Decreases pioglitazone exposure; monitor glycemic control in diabetic patients.
  • Amitriptyline: May substantially increase amitriptyline concentrations; titrate dose based on clinical response. Minor interactions include a 12% decrease in digoxin AUC; no significant changes with propranolol, diltiazem, or venlafaxine.

Pharmacology

Mechanism of Action

Topiramate exerts its therapeutic effects through multiple mechanisms of action at the molecular and cellular levels, reflecting its polypharmacological profile rather than reliance on a single primary target. This multifaceted approach contributes to its broad efficacy in treating seizures and migraines by modulating neuronal excitability. Key actions include blockade of voltage-gated sodium channels, enhancement of GABA_A receptor-mediated inhibition, antagonism of /kainate glutamate receptors, and inhibition of specific isoforms. Topiramate blocks voltage-gated sodium channels, particularly by promoting their fast inactivation and reducing sustained high-frequency firing in neurons, which helps prevent the spread of seizure activity. This effect occurs at relatively weak binding affinities, with an IC50 of approximately 48.9 μM in neuronal models. Additionally, topiramate acts as a positive allosteric modulator at GABA_A receptors, enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) by increasing chloride influx and hyperpolarizing neurons; its binding here is stronger than at sodium channels, supporting anticonvulsant activity at lower concentrations. It also antagonizes AMPA and kainate subtypes of glutamate receptors (e.g., GluK1 with IC50 ≈ 0.46 μM), thereby attenuating excitatory synaptic transmission and reducing neuronal depolarization during hyperexcitable states. Furthermore, topiramate inhibits isoforms II, IV, and V, leading to reduced intracellular bicarbonate levels and mild . This inhibition contributes to its effects by downregulating activity and may also play a role in through altered and . The combined polypharmacology—without a dominant mechanism—underlies topiramate's versatility across and prophylaxis, though it may relate briefly to adverse effects like .

Pharmacokinetics

Topiramate exhibits rapid absorption after , achieving a of approximately 80%, which is unaffected by food intake. Peak plasma concentrations occur within 2 to 4 hours following a dose, and steady-state plasma levels are typically attained in 4 to 8 days in individuals with normal renal function. The apparent for topiramate ranges from 0.55 to 0.80 L/kg, reflecting its distribution primarily into total compartments. is concentration-dependent and low, varying between 15% and 41% over therapeutic concentrations of 0.5 to 250 μg/mL. Metabolism of topiramate is minimal and primarily hepatic, with about 15% to 20% undergoing of the sulfamate group and smaller fractions via and ; no metabolites exceed 5% of the administered dose, and there is negligible involvement of enzymes. Elimination occurs predominantly via the kidneys, with 70% to 80% of the dose excreted unchanged in urine; the mean plasma elimination is 21 hours, ranging from 19 to 25 hours in healthy adults. In patients with renal impairment, defined as creatinine clearance less than 70 mL/min/1.73 m², topiramate clearance is reduced by approximately 42% to 54%, necessitating a 50% reduction in the usual adult dose to maintain therapeutic levels and minimize accumulation.

Detection in Body Fluids

Topiramate detection in body fluids is essential for , compliance assessment, and toxicological investigations. In plasma, the established therapeutic range for effective antiseizure activity is 5–20 μg/mL, as recommended by the . This range guides dose adjustments to balance efficacy and minimize adverse effects, particularly in management. Analytical methods such as (HPLC) and liquid chromatography-tandem (LC-MS/MS) are commonly employed for plasma quantification due to their . LC-MS/MS, for instance, involves liquid extraction with , separation on a C18 column, and detection via in negative mode, achieving a lower limit of quantification as low as 20 ng/mL. In urine, topiramate is primarily detected as the unchanged parent drug, with approximately 70% of an administered dose excreted renally without metabolism. This facilitates straightforward identification in routine screening, with a typical detection window of up to 72 hours following the last dose, influenced by renal clearance and individual factors like hydration and glomerular filtration rate. Such analysis supports confirmation of recent exposure or overdose, where elevated concentrations may correlate with acute toxicity. For assessing chronic use, and nail analysis offers a longer retrospective window, capturing incorporation over months. LC-MS/MS methods enable simultaneous detection of topiramate alongside other antiepileptics in , with limits of detection around 0.01 ng/mg and limits of quantification at 0.02 ng/mg after extraction. Segmental has revealed concentrations of 0.19–0.93 ng/mg in chronic users, providing insights into usage patterns over time. In forensic contexts, topiramate's plasma elimination half-life of 20–30 hours in monotherapy aids in estimating ingestion timing during overdose investigations. Postmortem blood levels exceeding therapeutic ranges, such as 49 mg/L, have been documented in fatal cases, underscoring the drug's role in confirming cause of death.

History

Development and Approval

Topiramate was first synthesized in 1979 by researchers at Janssen Pharmaceutica, a subsidiary of Johnson & Johnson, as part of an effort to develop novel antidiabetic agents through structural analogs of fructose-1,6-diphosphate aimed at inhibiting the enzyme fructose-1,6-bisphosphatase. During preclinical screening, the compound unexpectedly demonstrated potent anticonvulsant activity in animal models, including the maximal electroshock seizure test in mice, prompting a shift in focus toward its potential as an antiepileptic drug. Development was subsequently advanced by Ortho-McNeil Pharmaceutical, another Johnson & Johnson affiliate, which conducted extensive preclinical studies evaluating its efficacy, safety profile, and neuroprotective properties. Key clinical evaluation occurred through a series of randomized controlled trials (RCTs) between 1993 and 1995, primarily targeting partial-onset s in adults. These multicenter, double-blind, -controlled phase III studies, such as the dose-ranging trial evaluating 200, 400, and 600 mg/day doses as adjunctive therapy, showed that topiramate significantly reduced frequency compared to , with reductions ranging from 28% to 47% across dose groups and responder rates (≥50% reduction) up to 44%. The trials enrolled hundreds of patients with inadequately controlled despite standard therapies, establishing topiramate's efficacy and tolerability, which supported its progression to regulatory submission. The U.S. (FDA) approved topiramate on December 24, 1996, under the brand name Topamax, for use as adjunctive therapy in adults with partial-onset seizures or primary generalized tonic-clonic seizures and in children with Lennox-Gastaut syndrome. In 2004, the FDA expanded approval to include prophylaxis of headaches in adults, based on subsequent trials demonstrating reduced migraine frequency. Generics were first approved in 2006 following successful challenges, enabling multiple manufacturers, including Pharmaceuticals, to launch generic topiramate formulations that year and capture significant market share; the primary U.S. expired in 2008.

Regulatory Updates

In 2008, the U.S. (FDA) issued an alert regarding an increased risk of suicidal thoughts and behaviors associated with antiepileptic drugs, including topiramate, based on an analysis of 199 placebo-controlled trials involving 43,892 patients. This led to the addition of a to the prescribing information for topiramate and other antiepileptics in December 2008, emphasizing the need for close monitoring of patients for emerging signs of suicidality. In March 2011, the FDA updated the categorization of topiramate to Category D, indicating positive evidence of human fetal risk based on new data showing an increased incidence of oral clefts in infants exposed . This change was reflected in the approved labeling by July 2011, advising against use during unless benefits outweigh risks and recommending effective contraception for women of childbearing potential. In July 2012, the FDA approved Qsymia, a fixed-dose combination of phentermine and extended-release topiramate, for chronic in obese or adults with at least one weight-related , marking an expanded indication for topiramate beyond and prophylaxis. This approval included requirements for a Risk Evaluation and Mitigation Strategy (REMS) program to educate prescribers and patients on potential risks such as teratogenicity and effects. In October 2023, the (EMA) introduced a Pregnancy Prevention Programme for topiramate; in June 2024, the Medicines and Healthcare products (MHRA) in the UK aligned with this by implementing similar measures, contraindicating its use in and in women of childbearing potential unless specific conditions are met, including monthly pregnancy testing, use of highly effective contraception, and documentation of risk discussions. This measure was prompted by evidence of significant risks, including a 17-fold increased chance of oral clefts and potential neurodevelopmental disorders in exposed offspring. In September 2025, Medsafe, New Zealand's medicines regulatory authority, imposed restrictions on topiramate for prophylaxis, contraindicating it in and in women of childbearing potential who are not using highly effective contraception, aligning with global efforts to minimize fetal exposure risks. In the United States, topiramate itself is not classified as a under the , though the Qsymia combination is designated as Schedule IV due to the phentermine component; globally, it remains widely prescribed, with approximately 9.6 million prescriptions filled in the U.S. in 2023.

Research

Established Findings

A 2013 Cochrane systematic review of anti-seizure medications for Lennox-Gastaut syndrome (LGS) confirmed topiramate's effectiveness as an adjunctive therapy, demonstrating a significant reduction in drop seizures compared to placebo in randomized controlled trials involving over 200 participants. A 2014 meta-analysis of randomized controlled trials provided preliminary evidence suggesting topiramate's potential role in reducing alcohol cravings among individuals with alcohol dependence, with a small effect size (Hedges' g = 0.312, p = 0.07) across seven studies encompassing 1,125 patients, though the result was not statistically significant. These analyses also noted associated reductions in heavy drinking days, though benefits were less consistent for achieving complete abstinence. A 2020 review article on adjunctive therapies for bipolar disorder concluded that topiramate offers limited benefit over placebo in managing acute mania symptoms, based on pooled data from placebo-controlled trials showing no significant difference in Young Mania Rating Scale scores after 3-6 weeks of treatment in adults. Similarly, a 2016 Cochrane review reinforced this finding, reporting low-quality evidence that topiramate as an add-on to mood stabilizers did not outperform placebo adjuncts in reducing manic episodes, with response rates around 40% in both groups across five trials. Clinical trials evaluating topiramate as monotherapy for in obese adults have confirmed sustained reductions of 4-6% of baseline body weight at 96 weeks, as observed in a multicenter, double-blind study where participants on 96 mg daily doses achieved an average 5.1% loss compared to 1.2% with , alongside improvements in metabolic markers like fasting glucose. These results highlight topiramate's potential for long-term , though tolerability issues such as led to higher dropout rates in the active arm. These established findings underscore key therapeutic applications of topiramate while revealing gaps in efficacy for certain conditions, prompting ongoing investigations into optimized dosing and patient selection.

Emerging Investigations

Recent studies from 2024 and 2025, drawing on data from epilepsy-pregnancy registries, have reaffirmed the elevated risk of oral clefts associated with topiramate exposure during early pregnancy, underscoring the continued need for pregnancy prevention programs (PPPs) in women of childbearing potential prescribed the drug. For instance, updated registry analyses indicate that prenatal exposure to topiramate carries one of the highest malformation risks among antiseizure medications, with persistent associations to cleft lip and/or palate observed even at lower doses. These findings, based on large prospective cohorts, highlight the importance of enhanced counseling and contraception to mitigate teratogenic effects, as the baseline risk of oral clefts in the general population remains significantly lower. In migraine prevention, a phase 3 head-to-head published in 2025 demonstrated the superiority of over topiramate, with achieving greater reductions in monthly days and fewer treatment discontinuations due to adverse events. The double-blind study (NCT05748483) involved adults with episodic or chronic , showing that over 24 weeks, only 12.1% of -treated participants discontinued due to adverse events compared to 29.6% in the topiramate group, alongside superior efficacy across multiple endpoints such as ≥50% response rates. This comparison positions (CGRP) antagonists like as potentially preferable alternatives for long-term prophylaxis, given topiramate's higher tolerability burden. Ongoing investigations into topiramate's role in (PTSD), particularly among veterans with comorbid alcohol use disorder (AUD), have yielded preliminary evidence of symptom reduction when combined with prolonged exposure (PE) therapy. A 2025 randomized, double-blind, -controlled trial (NCT03176953) found that adding topiramate to PE resulted in more rapid and pronounced decreases in PTSD symptoms during the 12-week active treatment phase compared to PE plus placebo, with effects observed in outpatient veterans. Specifically, the topiramate augmentation group showed greater improvements on the Clinician-Administered PTSD Scale, though long-term benefits at 6-month follow-up were not sustained beyond the treatment period. These results suggest topiramate's potential as an adjunct for accelerating PTSD remission in this population, warranting further trials to assess durability and standalone efficacy. Pilot data from 2015 have explored topiramate's adjunctive role in managing withdrawal, building on its established use in substance-related disorders. Small-scale studies indicate that topiramate may alleviate cravings and withdrawal symptoms in individuals abusing , an with addictive potential, by modulating pathways. In one case series, topiramate administration led to complete resolution of cravings in patients with dependence, supporting its off-label application as a supportive during . These preliminary findings, though limited by sample size, highlight topiramate's versatility in addressing substance withdrawal syndromes, with calls for larger controlled trials to confirm efficacy.

References

  1. https://www.ncbi.nlm.nih.gov/books/NBK554530/
  2. https://go.drugbank.com/drugs/DB00273
  3. https://medlineplus.gov/druginfo/meds/a697012.html
  4. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020505s065,020844s056lbl.pdf
  5. https://pubmed.ncbi.nlm.nih.gov/8649570/
  6. https://www.neurology.org/doi/10.1212/WNL.52.7.1338
  7. https://www.neurology.org/doi/10.1212/WNL.52.7.1330
  8. https://pubmed.ncbi.nlm.nih.gov/10371538
  9. https://pubmed.ncbi.nlm.nih.gov/9092957/
  10. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/020505s067%2C020844s058lbl.pdf
  11. https://www.aafp.org/pubs/afp/issues/2005/1015/p1563.html
  12. https://jamanetwork.com/journals/jama/fullarticle/198261
  13. https://publications.aap.org/pediatrics/article/123/3/924/71669/Randomized-Double-Blind-Placebo-Controlled-Study
  14. https://news.abbvie.com/2025-06-18-AbbVie-Announces-New-Data-Demonstrating-Atogepant-QULIPTA-R-AQUIPTA-R-Achieves-Superiority-Across-All-Endpoints-in-Phase-3-Head-to-Head-Study-Compared-to-Topiramate-for-Migraine-Prevention
  15. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022580s000lbl.pdf
  16. https://www.nejm.org/doi/full/10.1056/NEJMp1211277
  17. https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2003.102
  18. https://pmc.ncbi.nlm.nih.gov/articles/PMC10532729/
  19. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00883/full
  20. https://jamanetwork.com/journals/jama/fullarticle/209129
  21. https://pmc.ncbi.nlm.nih.gov/articles/PMC4047180/
  22. https://pmc.ncbi.nlm.nih.gov/articles/PMC12093777/
  23. https://pmc.ncbi.nlm.nih.gov/articles/PMC12349977/
  24. https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/1744-859X-4-5
  25. https://pmc.ncbi.nlm.nih.gov/articles/PMC4985391/
  26. https://pmc.ncbi.nlm.nih.gov/articles/PMC8406931/
  27. https://www.sciencedirect.com/science/article/abs/pii/S0006322306010092
  28. https://pubmed.ncbi.nlm.nih.gov/26894822/
  29. https://pmc.ncbi.nlm.nih.gov/articles/PMC5798655/
  30. https://www.biospace.com/fda-risk-of-oral-birth-defects-in-children-born-to-mothers-taking-topiramate-made-by-mylan-pharmaceuticals-inc-and-ortho-mcneil-inc
  31. https://www.hsa.gov.sg/announcements/safety-alert/topiramate-%28topamax-%29-and-risk-of-birth-defects
  32. https://www.ema.europa.eu/en/medicines/human/referrals/topiramate
  33. https://www.gov.uk/drug-safety-update/topiramate-topamax-introduction-of-new-safety-measures-including-a-pregnancy-prevention-programme
  34. https://www.medicines.org.uk/emc/rmm/3084/Document
  35. https://assets.publishing.service.gov.uk/media/66740dba64e554df3bd0dbca/DSU_-_June_2024.pdf
  36. https://www.nhs.uk/medicines/topiramate/common-questions-about-topiramate/
  37. https://www.healthcentral.com/condition/migraine/topamax-and-female-hormones
  38. https://journals.sagepub.com/doi/pdf/10.1177/0333102414529669
  39. https://pubmed.ncbi.nlm.nih.gov/36641095/
  40. https://nhssomerset.nhs.uk/wp-content/uploads/sites/2/SCP-Topiramate-v1.1-March-2025.pdf
  41. https://www.medsafe.govt.nz/safety/DHCPLetters/TopamaxApril2025.pdf
  42. https://www.eclipsesolutions.org/UploadedFiles/821_2025%252001%2520Update%2520for%2520Primary%2520Care%2520Topiramate%2520New%2520Pregnancy%2520Prevention%2520Programme%2520V1.pdf
  43. https://www.mayoclinic.org/diseases-conditions/drug-allergy/expert-answers/sulfa-allergy/faq-20057970
  44. https://www.mayoclinic.org/drugs-supplements/topiramate-oral-route/precautions/drg-20067047
  45. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2829265
  46. https://www.seizure-journal.com/article/S1059-1311(22)00074-7/fulltext
  47. https://pubmed.ncbi.nlm.nih.gov/9300637/
  48. https://www.sciencedirect.com/science/article/abs/pii/S0304394097005430
  49. https://www.rndsystems.com/products/topiramate_3620
  50. https://pubmed.ncbi.nlm.nih.gov/10768298/
  51. https://www.tandfonline.com/doi/full/10.1517/14728214.2012.664132
  52. https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20505S3_Topamax_clinphrmr.pdf
  53. https://pubmed.ncbi.nlm.nih.gov/12973408/
  54. https://pmc.ncbi.nlm.nih.gov/articles/PMC10863906/
  55. https://pubmed.ncbi.nlm.nih.gov/18348335/
  56. https://pmc.ncbi.nlm.nih.gov/articles/PMC11352693/
  57. https://www.thehopehouse.com/topiramate-addiction/withdrawal-detox/
  58. https://pubmed.ncbi.nlm.nih.gov/33091538/
  59. https://pubmed.ncbi.nlm.nih.gov/8827398/
  60. https://pubmed.ncbi.nlm.nih.gov/20494535/
  61. https://pmc.ncbi.nlm.nih.gov/articles/PMC6494007/
  62. https://pmc.ncbi.nlm.nih.gov/articles/PMC4948003/
  63. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205122Orig1s000ChemR.pdf
  64. https://pubmed.ncbi.nlm.nih.gov/9092954/
  65. https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020505_000_aprvl_ltr.pdf
  66. https://investor.mylan.com/news-releases/news-release-details/mylan-announces-final-fda-approval-topiramate-tablets
  67. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-risk-oral-clefts-children-born-mothers-taking-topamax-topiramate
  68. https://www.medsafe.govt.nz/safety/Alerts/Topiramate-pregnancy.asp
  69. https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf
  70. https://clincalc.com/drugstats/Drugs/Topiramate
  71. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003277.pub3/full
  72. https://jamanetwork.com/journals/jama/fullarticle/2811435
  73. https://www.psychiatrictimes.com/view/topiramate-bipolar-disorder-comorbidities-the-myths-evidence
  74. https://pmc.ncbi.nlm.nih.gov/articles/PMC6457604/
  75. https://clinicaltrials.gov/study/NCT00236600
  76. https://www.jwatch.org/na59025/2025/07/31/new-data-major-malformations-prenatal-antiseizure
  77. https://www.drugs.com/pregnancy/topiramate.html
  78. https://www.neurologyadvisor.com/news/atogepant-outperforms-topiramate-in-head-to-head-migraine-prevention-study/
  79. https://www.healio.com/news/neurology/20250701/fewer-discontinuations-mean-monthly-migraine-days-with-atogepant-vs-topiramate
  80. https://www.neurologylive.com/view/cgrp-therapy-atogepant-outperforms-topiramate-head-to-head-temple-trial
  81. https://pubmed.ncbi.nlm.nih.gov/40103353/
  82. https://psychiatryonline.org/doi/abs/10.1176/appi.ajp.20240470
  83. https://www.researchgate.net/publication/389982133_A_Randomized_Clinical_Trial_of_Prolonged_Exposure_Therapy_With_and_Without_Topiramate_for_Comorbid_PTSD_and_Alcohol_Use_Disorder
  84. https://www.physiciansweekly.com/post/prolonged-exposure-therapy-with-topiramate-for-ptsd-and-alcohol-use-disorder
  85. https://pubmed.ncbi.nlm.nih.gov/26441400/
  86. https://pubmed.ncbi.nlm.nih.gov/26554372/
  87. https://www.researchgate.net/publication/309101363_Topiramate_in_Dextromethorphan_Abuse
Add your contribution
Related Hubs
Contribute something
User Avatar
No comments yet.